The pathophysiology of functional (psychogenic) movement disorders (FMD) is very poorly understood. These disorders are common in the population, diagnosis is difficult and treatment typically ineffective. We are studying the mechanisms underlying these disorders using cognitive tasks, neurophysiological testing, psychiatric measures, and functional imaging. One functional imaging study was an fMRI investigation of patients with tremor, and results showed abnormally reduced activation in the temporoparietal junction region. We are also looking for abnormal activations related to tasks that probe functions such as emotional expression and movement inhibition, and have already shown abnormal activation in the amygdala. Recently, we have been studying fear conditioning, which is mediated by the amygdala. We have also investigated these patients for their sense of agency during fMRI studies, similar to the way we have studied normal subjects. In a large on-going study, with psychiatric help, we are exploring the biopsychosocial underpinnings of functional movement disorders. We showed that there is no abnormality of diurnal cortisol levels; however, studies of heart rate variability show abnormal vagal function. Neuroimaging studies show some abnormal connectivity even at rest, including from the temporoparietal junction region. We are currently studying changes in structural MRI in these patients. We are also pursuing genetic and epigenetic abnormalities in a pilot study. For many years, we have been collecting families with essential tremor looking for possible genetic abnormalities. This work is being pursued with additional sequencing in conjunction with other NIH investigators. While it is known that many patients with essential tremor respond to ethanol, it is not clear how many and what the physiology of the response is. We are investigating this including TMS measures of cortical excitability. We have also been looking at the clinical neurophysiology of essential tremor and comparing it with similar measures in dystonic tremor.